Langerhans cell histiocytosis: an uncommon presentation, successfully treated by thalidomide

Langerhans cell histiocytosis (LCH) is a rare disease and generally affects children under 15 years of age. Adult onset form and cutaneous features at presentation are uncommon. There are some options for treatment of the skin lesions of LCH such as topical and intralesional corticosteroid, nitrogen mustard, etc., which are not completely curative. Herein, we report a case of perianal LCH in a 20-year-old man with one-year history of recalcitrant well-demarcated, erythematous, and ulcerated plaque surrounding the anal orifice, with pain and difficulty in defecation that was successfully treated with thalidomide.     

Adult Langerhans cell histiocytosis limited to the skin

BACKGROUND: The incidence of Langerhans cell histiocytosis (LCH) is 4-5 per million in children with only 30% of this number having an adult onset. While dermatological manifestations occur in as many as 50% of cases, disease limited to the skin is uncommon among reported cases of adult LCH. OBJECTIVES AND METHODS: To present 3 new cases of adult LCH and a review of the literature of isolated cutaneous LCH in adults. RESULTS: Three adults with scalp, vulvar and generalized LCH lesions had refractory responses to treatment. CONCLUSIONS: LCH may present with unusual cutaneous manifestations limited to the skin in adults. Optimal treatment has not yet been determined.     

Co‐existence of Langerhans cell histiocytosis and reticulohistiocytosis with initial presentation of skull lesions: A case report

Langerhans cell histiocytosis (LCH) is a rare histiocytic disorder resulting from dysregulated clonal proliferation of Langerhans cells. Reticulohistiocytosis (RH) is another rare histiocytosis caused by the proliferation of histiocytes other than Langerhans cells. Co‐existence of LCH and RH in different organs and in the same skin area has not been reported. We present the case of a 20‐year‐old woman who initially had co‐existing bone LCH and cutaneous RH. After 1 year of chemotherapy with cytarabine, bone LCH significantly improved but cutaneous LCH developed in the same area where cutaneous RH was, resulting in hybrid LCH and RH of the skin. This unique history provides some evidence to support the theory that LCH and RH originate from the same stem cells and subsequently develop into hybrid LCH and RH of the skin in a cytokine environment influenced by chemotherapy. Repeat skin biopsies may be considered for adjusting treatment regimens in LCH patients whenever pre‐existing skin lesions progress.     

Langerhans cell histiocytosis associated with breast carcinoma successfully treated with topical imiquimod

Langerhans cell histiocytosis (LCH) encompasses a group of disorders characterized by the proliferation and infiltration of Langerhans cells within internal organs and/or skin. There is often multiorgan involvement; isolated cutaneous LCH is less common. ¹ The aetiology of cutaneous LCH remains uncertain, and debate remains as to whether LCH represents a neoplastic condition or is simply reactive. We report a 53‐year‐old woman who developed isolated cutaneous LCH 15 months after being diagnosed with infiltrating ductal carcinoma of the left breast. The LCH was treated with topical imiquimod, resulting in clinical and histological resolution. Our case highlights the rare association between cutaneous LCH and breast carcinoma, and the clinical and histological response that can be achieved with topical imiquimod. After a diagnosis of LCH, patients require long‐term follow‐up, due to the risk of recurrence and/or development of a subsequent malignancy.     

Juvenile xanthogranuloma as a sequel to Langerhans cell histiocytosis: a report of three cases

We report three children who had multisystem Langerhans cell histiocytosis (LCH) with cutaneous involvement and subsequently developed juvenile xanthogranuloma (JXG). JXG appeared 3--6 years after the initial manifestation of LCH. JXG lesions, which presented as yellowish papules, revealed typical Touton giant cells and were factor XIIIa positive but S100 and CD1a negative. Non-LCH histiocyte disorders, such as JXG, are known to occur as a reaction to a variety of external stimuli such as infection and trauma. It is therefore conceivable that the inflammatory reaction associated with LCH may have precipitated the development of JXG in our patients. Alternatively, one could speculate that this association might be due to a common histogenetic precursor of the cell types involved.     

Treatment of congenital Langerhans cell histiocytosis with cobimetinib

We report a case of congenital multisystem Langerhans cell histiocytosis with cutaneous and hematopoietic involvement. After the failure of first-line (vinblastine and prednisolone) and second-line (vincristine and cytarabine) therapies, treatment with cobimetinib, a mitogen-activated protein kinase (MEK) inhibitor, led to the remission of disease and a sustained response after 11 months of ongoing treatment. Protein kinase inhibitors targeting BRAF or MEK could represent a promising future therapeutic option, also in children with LCH.     

Extensive cutaneous Langerhans cell histiocytosis in an elderly woman

Langerhans cell histiocytosis (LCH), especially with involvement limited to the skin in adults is a rare entity. Primary cutaneous LCH in older patients usually follows a benign course and can regress spontaneously. We report a fatal case of disseminated cutaneous LCH in an elderly woman. A 64‐year‐old woman presented with confluenced erythematous macule and diffuse papuloscaling and papulocrusted lesions on the trunk that became erosive on the area of axillae and groins. Histopathological study of skin specimens showed extensive epidermotropic and folliculotropic, lichenoid infiltration of Langerhans' cells. Positive immunohistochemical staining for CD1a and S‐100 protein in Langerhans' cells, and numerous typical Birbeck granules in the cytoplasm of Langerhans' cells by electron microscopy study confirmed the diagnosis of LCH. Chest X‐rays and computed tomography scans showed mild interstitial pneumonia without a honeycomb appearance. The patient was diagnosed with LCH. Her general condition worsened rapidly and she died 1 month after diagnosis. Because extracutaneous involvement of LCH had been ruled out by laboratory and imaging investigations, we would like to believe this case should be classified as “malignant” LCH based on the clinical course.     

Adult‐onset systemic Langerhans cell histiocytosis mimicking inflammatory bowel disease: the value of skin biopsy and review of cases of Langerhans cell histiocytosis with cutaneous involvement seen at the Mayo Clinic

Background

Langerhans cell histiocytosis (LCH) is frequently known to involve multiple organ systems. However, gastrointestinal involvement by LCH is rare.

Methods

We describe a 68‐year‐old woman with a 3‐year history of intermittent diarrhea initially diagnosed as inflammatory bowel disease. She was subsequently found to have systemic LCH with involvement of the gastrointestinal tract, lungs, liver, and skin after skin biopsy was performed. A retrospective review of patients with cutaneous involvement of LCH seen at the Mayo Clinic over the past 15 years was conducted. The presence of systemic disease as well as specific organ system involvement was reviewed.

Results

Twenty‐four patients with cutaneous LCH were identified. Besides our case, one other patient with both gastrointestinal and cutaneous involvement was identified. This patient died at six months of age. No other adult‐onset cases were identified.

Conclusions

Gastrointestinal involvement with LCH is rare, can be easily misdiagnosed, and likely portends a poor prognosis. In patients with ill‐defined systemic symptoms, cutaneous exam and biopsy have the potential to diagnose systemic disease.     

Xanthomas in a patient with Langerhans cell histiocytosis and liver cirrhosis

Skin involvement in acute forms of Langerhans cell histiocytosis (LCH) is in the form of erythematous papules, although rare forms of xanthomatous lesions have been described. We present the case of a boy with acute disseminated LCH who, at the age of 16 months, began to experience outbreaks of seborrheic dermatitis-like skin lesions and progressive hepatic dysfunction. The symptoms were complicated by partial central diabetes insipidus and specific pulmonary infiltration by Langerhans cells, which led to fibrosis. During the course of the disease, the patient developed liver cirrhosis, alterations in the lipid profile and disseminated xanthomatous skin lesions, concomitant with the lesions specific to the LCH. Despite successive cycles of chemotherapy, the outcome was the death of the patient after five years, due to his liver disease. Xanthomatous lesions in LCH are typical of the late stages of chronic progressive forms, such as Hand-Schüller-Christian disease. When they appear in acute disseminated forms, there is some controversy over whether they correspond to a progression of the disease towards more chronic forms, or whether they are associated independent lesions, such as in this case.     

Langerhans cell histiocytosis mimicking lichen nitidus with bone involvement

We report the case of a 6‐month‐old Hispanic boy with a 4‐month history of widespread pruritic hypopigmented papules mimicking lichen nitidus. The final diagnosis was multisystem non‐risk‐organ Langerhans cell histiocytosis (LCH), with cutaneous and multiple bone involvement. With this patient and others previously reported in the literature, we suggest an early biopsy of the hypopigmented rash in children.     

Assessment of the extent of cutaneous involvement in children and adults with mastocytosis: relationship to symptomatology,tryptase levels,and bone marrow pathology

BACKGROUND: Cutaneous involvement occurs in most patients with systemic mastocytosis. OBJECTIVE: We sought to determine whether the extent of cutaneous involvement is predictive of systemic disease. METHODS: In a prospective survey of 48 adults and 19 children, the extent and density of cutaneous lesions were compared with patient history, symptoms, internal organ involvement, serum total mast cell tryptase level, and bone marrow pathology. RESULTS: Cutaneous lesions in children were of a greater mean and maximum diameter, but similar in extent and density compared with lesions in adults. In adults with skin lesions, the extent of lesions correlated to disease duration. Adults with extensive cutaneous disease experienced more pruritus and flushing. Fatigue, splenomegaly, and hepatomegaly were more frequent in adults without cutaneous involvement; and in those with a greater density of lesions and disease duration. Increased tryptase levels were found in children and adults with systemic disease and correlated to skin lesion density and bone marrow pathology. CONCLUSION: An examination of the extent and density of cutaneous lesions in adults helps identify those with more extensive extracutaneous disease and, thus, requiring a more thorough evaluation.     

Langerhans cell histiocytosis of skin: a clinicopathologic analysis of five cases

BACKGROUND AND AIMS: Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of histiocytes characterized by a proliferation of abnormal and clonal Langerhans cells. We retrospectively studied clinicopathologic features of this disorder in five cases. METHODS: Clinical and histopathological findings of five cases of cutaneous LCH were reviewed based on the hospital records. RESULTS: The age of patients ranged from 28 days to 5 years and M: F ratio was 1:1.5. Clinically, the diagnoses suggested were histiocytosis, varicella, transient neonatal pustular melanosis, keloid, sarcoidosis, seborrheic keratosis and LCH. The most common type of skin lesion was a generalized papular lesion. Histologically, all cases showed aggregates of large mononuclear histiocytes (Langerhans cells) with reniform, irregular, cleaved nuclei and abundant eosinophilic cytoplasm. There was multi-systemic involvement in two patients and single-system involvement in three patients. CONCLUSION: Cutaneous lesions may be the sole presenting feature of LCH. Diagnosis is based on demonstration of S-100 positive histiocytes.     

Multisystem Langerhans cell histiocytosis in adult

Langerhans cell histiocytosis (LCH), is a rare disorder, clinically presents with heterogeneous manifestations, and has an unpredictable outcome. Commonly seen in infancy or early childhood, the disorder is characterized by proliferation of abnormal and clonal Langerhans cell in skin, bone, lymph nodes, lungs, liver, spleen, and bone marrow. Occurrence of LCH in adults is rare. Here, we report the case of an adult with acute onset of polymorphic eruptions all over the body, which on biopsy showed features of multisystem LCH, and was confirmed by immunohistochemistry. Although multisystem LCH has a poor prognosis, our patient responded well to chemotherapy.     

Kutane Varianten der Langerhans-Zell-Histiozytose im frühen Kindesalter

The term Langerhans cell histiocytosis (LCH) has been endorsed to describe a group of rare entities, a highly variable spectrum of clinical presentations which are all characterized by localized or generalized proliferation of pathological Langerhans cells. We describe two infants with LCH who had very distinct cutaneous lesions. A two month-old infant developed discrete, disseminated red-brown nodules and plaques. In contrast, a second child at the age of nine months presented with brown aggregated scaling, crusted and ulcero-necrotic papules mainly restricted to the abdomen. In both patients, dermatohistopathology showed characteristic proliferation of pathologic Langerhans cells, and staging procedures revealed involvement of lung and bones. These two cases illustrate the marked variability of clinical presentation and disease course of LCH. In addition, important aspects and current concepts of LCH are discussed reviewing relevant and recent literature.     

Treatment of adult Langerhans cell histiocytosis with etoposide.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a reactive disease in which abnormal Langerhans cells accumulate in various body sites and cause damage to affected organs. Adults often do not respond to conventional therapy with local or systemic steroids. OBJECTIVE: Our purpose was to investigate intravenous etoposide as monotherapy in the treatment of adult patients with severe or resistant LCH. METHODS: In an open study, three adult patients with LCH (one with single-system skin disease and two with multisystem disease) were treated with etoposide, 100 mg/m2/day, for 3 days. This was repeated every 3 or 4 weeks for three or four cycles. RESULTS: All patients achieved clinical remission that persisted during a 12- to 14-month follow-up. No serious side effects were noted. CONCLUSION: We recommend the use of etoposide monotherapy in severe or restricted LCH in adults.     

Langerhans cell histiocytosis associated with lichen sclerosus of the vulva: case report and review of the literature

Langerhans cell histiocytosis (LCH) is characterized by a clonal proliferation of bone marrow‐derived Langerhans cells. While cutaneous involvement is relatively common, LCH restricted to the vulvar area is a rare phenomenon and can occur in different clinical settings. Occasionally, vulvar LCH heralds subsequent multi‐organ involvement with an aggressive clinical course. Even cases of LCH isolated to the vulvar area can present with local recurrences despite excision and radiation. We present a case of a 68‐year‐old female with a 1‐month history of pruritic lesions on her vulva. Physical examination showed whitish plaques with scattered nodular areas on the labia majora. A vulvar biopsy showed a background of lichen sclerosus (LS) with foci of oval to polygonal cells with moderately abundant eosinophilic cytoplasm and folded nuclei showing frequent nuclear grooves. Immunohistochemical staining showed that the cells were positive for CD1a and S‐100, confirming the diagnosis of LCH. On further workup, there was no evidence of disseminated disease involving other organs. While vulvar LCH is uncommonly seen, and with only one previous case report in the literature associated in the setting of lichen sclerosus, this case illustrates the importance of recognizing this condition and ensuring proper clinical follow‐up to rule out a systemic involvement.     

Narrowband Ultraviolet B Light in Langerhans Cell Histiocytosis: A Case Report

Langerhans cell histiocytosis (LCH) (previously called eosinophilic granuloma, Hand–Schüller–Christian syndrome, Letterer–Siwe disease, and Hashimoto–Pritzker disease) is a rare, heterogeneous disorder with highly variable presentation. LCH commonly affects the skin, as well as internal organs. Because the skin lesions appear benign, and LCH is unfamiliar to most physicians, diagnosis is often delayed. Treatment is controversial, with further clinical study needed. For persons with extensive, skin‐limited disease, the existing topical therapies are impractical. We present a child with cutaneous LCH lesions that responded to ultraviolet light phototherapy with minimal adverse effects or patient discomfort.     

Langerhans cell histiocytosis: A retrospective analysis in a Korean tertiary hospital from 2003 to 2012

Epidemiological study of Langerhans cell histiocytosis (LCH) has been limited due to its rarity and multisystemic involvement. The aim of this study was to investigate the epidemiological features of LCH via the clinical data warehouse (CDW). Clinical data of 30 LCH patients from the all departments of a tertiary referral hospital between 2003 and 2012 were analyzed retrospectively by searching the CDW. The male‐to‐female ratio was 2.8:1. The age of onset ranged 7 days to 57 years with a median of 13 years. Of the patients, 36.7% presented initial symptoms before the age of 10 years. The involved organs at diagnosis were: bone (66.7%), skin (16.7%), lungs (13.3%) and lymph node (3.3%). For all of the 30 cases, there were 31 disease sites because of a single case of multisystemic disease involving both skin and bone. Of the 96.7% of patients with single‐system disease, 69.0% had bony involvement. This study elucidated the clinical features of LCH from all the departments of a tertiary hospital via the CDW, which suggests a potential role of the CDW as a new epidemiological approach for rare diseases.     

Sinus Histiocytosis Clinically Limited to the Skin

Sinus histiocytosis with massive lymphadenopathy is a rare clinicopathologic entity that affects mainly children and young adults. Although the lymph nodes are the most common sites of involvement, extranodal infiltrates may arise in the orbits, skin, upper respiratory tract, and bone, as well as other organs. Approximately 10% of patients have had cutaneous infiltrates, but very few of them have had lesions limited to the skin. We treated a 15-year-old female with cutaneous nodules as the sole manifestation of the disease.     

Extensive nail changes in a toddler with multisystemic Langerhans cell histiocytosis

Langerhans cell histiocytosis (LCH) is a multisystem disorder involving various organs. Nail changes in LCH are extremely rare. We present this case report of extensive nail changes in an 18‐month‐old child with multisystem LCH.